:The importance of adequate enteral nutrition during the first few weeks following birth in premature very low birth weight (VLBW) infants is well known and necessary to facilitate optimal growth and development and reduce both premature birth-related and iatrogenic complications. Routine aspiration of potential residual gastric contents (RGC) has traditionally been performed prior to every feeding in these infants. Increased volumes have been thought to be related to feeding intolerance or an early symptom of necrotizing enterocolitis. In critically ill children and adults increased volumes have also bee thought to be associated with respiratory aspiration of gastric secretions. However, there is no conclusive evidence that this practice improves care or reduces complications and may actually contribute to complications including a delay in achievement of full enteral feedings. Potential complications related to delaying attainment of full enteral feedings include increased use of parenteral nutrition (PN), parenteral nutrition associated liver disease (PNALD), poor growth, more hours requiring a central venous line (CVL), increased risk of late onset sepsis (LOS), prolonged hospitalization, as well as disturbances in gastrointestinal (GI) integrity and function. The overall objective of this 4-year study is to determine whether omission of routine aspiration of potential RGC improves nutritional outcomes of VLBW premature infants. The proposed study will follow a prospective cohort (N = 120) of racially and economically diverse premature VLBW infants for 6 weeks following birth. Aim 1 will determine the risks and benefits of aspirating RGC and the clinical benefits of omitting aspiration of RGC prior to enteral feedings on nutritional outcomes of premature VLBW infants including weekly enteral intake, time to reach full enteral feedings, growth indices, hours of TPN, incidence of PNALD, hours with a CVL, incidence of LOS, and length of stay. For Aim 2, the effect of routine RGC aspiration on GI mucosal bleeding and inflammation will be determined through measurement of blood and calprotectin in the stool. The effect of aspiration of RGC on GI function will be measured using serum levels of the peptides gastrin and motilin in Aim 3. All enrolled infants will receive the same care with one exception. Those randomly assigned to the Control Group will continue to have routine aspiration of potential RGC prior to every feeding and those in the Experimental Group will not. Outcomes measures will be monitored over 6 weeks. Results are expected to fill an important gap in research regarding the necessity of aspirating RGC prior to feeding in premature VLBW infants, whether aspiration of RGC influences short and long term outcomes and whether routine aspiration of RGC is detrimental to premature VLBW infants. Public Health Relevance: This research has potential to influence health policy and practices that may directly translate to improved nutritional and health outcomes for premature VLBW infants.